Tumor-Derived Lactate Modifies Antitumor Immune Response: Effect on Myeloid-Derived Suppressor Cells and NK Cells

In this study, we explore the hypothesis that enhanced production of lactate by tumor cells, because of high glycolytic activity, results in inhibition of host immune response to tumor cells. Lactate dehydrogenase-A (LDH-A), responsible for conversion of pyruvate to lactate, is highly expressed in tumor cells. Lentiviral vector-mediated LDH-A short hairpin RNA knockdown Pan02 pancreatic cancer cells injected in C57BL/6 mice developed smaller tumors than mice injected with Pan02 cells. A decrease occurred in the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of mice carrying LDH-A-depleted tumors. NK cells from LDH-A-depleted tumors had improved cytolytic function. Exogenous lactate…